The mission of the High-throughput Library Screening (HTLS) Core is to bring chemical biology, functional genomics and early phase drug discovery to NINDS USERs. Chemical biology and functional genomics together bring a powerful approach to deciphering signaling pathways that control complex biological problems, and though high throughput screening (HTS) develop novel pharmacological compounds for in vivo applications, such as studying the neurological function of newly discovered proteins and validating candidate compounds as drug candidates. This core will support NINDS investigators' development of druggable targets and lead compounds for new treatments of neurological disorders. The cornerstone of this core is the existing high-throughput (HT) library screening and functional genomics capability of the Sanford-Burnham Medical Research Institute (SBMRI). HT library screening is not generally available to academic investigators, so this facility provides a new and unique approach toward characterizing proteins and signaling pathways involved in many aspects of neural development and neurologic disease. This core has been operational as part of the SBMRI Cancer Center for over six years and was heavily used by La Jolla neuroscientists under the auspices of the La Jolla Neuroscience Center NIH Blueprint Core Grant for the past four years, and without this grant there would have been no access to the HTS Core Facility by neuroscientists. The present NINDS P30 application will continue to permit high priority access to NINDS neuroscientists at internal charge-back rates. SBMRI has committed >$110 million investment in equipment, including the robotic screening facility and HT microscopes (for high-content screening), and chemical and siRNA/microRNA libraries, providing significant value-added benefit to NINDS.